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March 3, 2008 -- Tamoxifen, a widely used breast cancer drug, appears to help treat the manic phase of bipolar disorder. Researchers say the discovery should help them come up with even better drugs to treat bipolar patients.

In a newly published study from Turkey, roughly half the manic patients who took the drug tamoxifen got better during three weeks of treatment, compared to just 5% of placebo-treated patients.

About a quarter of the tamoxifen-treated patients and none of the placebo-treated patients achieved remissions.

The study was small, involving just 50 patients, but it is not the first to show that tamoxifen decreases manic symptoms associated with bipolar disorder.

Last fall, researchers with the U.S. government's National Institute of Mental Health (NIMH) came to the same conclusion in a trial involving 16 bipolar disorder patients who were manic.

Tamoxifen Targets Protein Kinase C

Tamoxifen has been used for more than two decades to treat breast cancer. It works by interfering with the activity of the hormone estrogen, which fuels breast cancer growth.

But it also inhibits a group of enzymes known as protein kinase C, and it was this action that first intrigued investigators studying bipolar disorder.

NIMH researcher Husseini Manji, MD, has been studying the role of protein kinase C (PKC) in bipolar disorder for more than a decade. His work led to the finding that PKC activity, which is involved in cell messaging, is accelerated during the manic phase of bipolar disorder.

"We've suspected for a while that a drug that inhibits protein kinase C would have an anti-manic effect in these patients," Manji tells WebMD. "Tamoxifen isn't perfect, but it fit the bill."

In the NIMH study, Manji and colleagues reported that 63% of patients had reduced manic symptoms when treated with tamoxifen after three weeks, compared to about one in eight placebo-treated patients.

The newly reported study from Turkey followed the same design as the NIMH trial.

Researcher Aysegul Yildiz, MD, and colleagues of Turkey's Dokuz Eylul University Medical School treated 50 manic bipolar patients with either tamoxifen or placebo for three weeks.

Patients in both groups were also treated with the antianxiety sedative lorazepam, as needed, to help control their symptoms.

At the end of three weeks of treatment, the tamoxifen-treated patients had significantly lower scores on tests designed to measure the severity of manic symptoms, while the scores of placebo-treated patients increased slightly.

Almost half (48%) of patients taking tamoxifen, compared to 5% of placebo-treated patients, responded to the treatment, meaning that they had reductions of at least half in mania scores.

Tamoxifen-treated patients also needed less lorazepam in the second and third weeks of the study.

The findings are published in the March issue of the Archives of General Psychiatry.

Better Treatments Needed for Manic Phase of Bipolar Disorder

About 6 million adults in the U.S. have bipolar disorder, a condition characterized by dramatic mood shifts from manic 'highs' to depressed 'lows.' Manic episodes can last from at least one week to months, and symptoms can include extreme restlessness, sleeplessness, irritability, and distractibility.

It is during this manic phase that bipolar patients most often engage in the risky, out-of-control, pleasure-seeking behaviors.

Yildiz tells WebMD that better treatments for the manic phase of bipolar disorder are badly needed, because current treatments typically take many weeks to work.

"During this time, people can lose their marriages, their jobs, or all their money," she says. "Finding quicker treatments would be very meaningful."

But while tamoxifen is effective, its estrogen-inhibiting action makes it problematic for the long-term treatment of bipolar patients, Manji says.

He adds that a drug that directly targets PKC activity but doesn't block estrogen receptors could represent a big step forward in the treatment of bipolar disorder and possibly other mental illnesses like posttraumatic stress disorder (PTSD) and even alcoholism.

Researchers are working to find such treatments and to target the exact PKC enzymes associated with mania.

"There are about 12 different subtypes of protein kinase C, and we think that two of those are important for the treatment of mania," he says. "If we come up with a treatment that just targets these two, it is likely to be much more effective with fewer side effects."